Hydrochloric Acid → 4-[1-(4-Cyano-3-fluorophenyl)-4-oxo-2-thioxo-1,3-diazaspiro[4.4]non-3-yl]-2-trifluoromethylbenzonitrile

HRID 245028Notes

Reaction equation

HRID 245028 reaction equation
[N:1]([C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[C:6]([C:12]([F:15])([F:14])[F:13])[CH:5]=1)=[C:2]=[S:3].[C:16]([C:18]1([NH:23][C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[C:26]([F:32])[CH:25]=2)[CH2:22][CH2:21][CH2:20][CH2:19]1)#N.C[OH:34].Cl>CN(C=O)C.O>[C:28]([C:27]1[CH:30]=[CH:31][C:24]([N:23]2[C:18]3([CH2:22][CH2:21][CH2:20][CH2:19]3)[C:16](=[O:34])[N:1]([C:4]3[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[C:6]([C:12]([F:13])([F:15])[F:14])[CH:5]=3)[C:2]2=[S:3])=[CH:25][C:26]=1[F:32])#[N:29]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 116155404-Isothiocyanato-2-(trifluoromethyl)benzonitrileHCID 671319804-(1-Cyanocyclopentylamino)-2-fluorobenzonitrile

Product 1

HCID 159516254-[1-(4-Cyano-3-fluorophenyl)-4-oxo-2-thioxo-1,3-diazaspiro[4.4]non-3-yl]-2-trifluoromethylbenzonitrileYield 7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 4-isothiocyanato-2-trifluoromethylbenzonitrile (1a) (0.171 g, 0.75 mmol) and 4-(1-cyanocyclopentylamino)-2-fluorobenzonitrile (54b) (0.115 g, 0.5 mmol) in dry DMF (1 ml) was heated under microwave irradiation at 60° C. for 48 hours. To this mixture were added methanol (3 ml) and aq 2M HCl (2 ml). The second mixture was refluxed for 1 hour. After being cooled to room temperature, the reaction mixture was poured into cold water (10 ml) and extracted with ethyl acetate (15 ml). The organic layer was dried over MgSO4, concentrated and chromatographed (dichloromethane:acetone, 98:2) to yield 4-[1-(4-cyano-3-fluorophenyl)-4-oxo-2-thioxo-1,3-diazaspiro[4.4]non-3-yl]-2-trifluoromethylbenzonitrile (54c) [RD168] (0.017 g, 0.037 mmol, 7%), of which the structure is illustrated in Formula 30, as an off-white powder.

Workup

  1. temperatureThe second mixture was refluxed for 1 hour
  2. temperatureAfter being cooled to room temperature
  3. extractionextracted with ethyl acetate (15 ml)
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customchromatographed (dichloromethane:acetone, 98:2)

Sources & evidence

ORD record
ord-8e6f88373ea44b0f92605ae9ece69ddf
Source dataset
uspto-grants-2014_02
Patent number
US08658681B2

Reaction notes

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